The single greatest impediment to cancer diagnosis is the general requirement that the tumor itself must be detected directly. Efforts to identify genetic abnormalities in normal tissues of patients with cancer or at risk of cancer have been disappointing. For example, BRCA1 mutations are present in only about 1% of breast cancers. A small fraction of patients with colorectal cancer have predisposing mutations in the APC gene (&gt;1%), causing adenomatous polyposis coli. An even smaller fraction show mutations in genes responsible for replication error repair (&gt;2% of colon cancer patients, or much less than 1% of the population), show mutations in genes responsible for nucleotide mismatch error repair causing hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome).
Genetic studies of colorectal cancer present a paradox, in that 15-40% of sporadically occurring tumors show DNA microsatellite instability, depending on the number of microsatellite markers that are used to detect it, even though the overwhelming majority of such tumors do not show mutations in known error repair genes. Furthermore, microsatellite instability in many common tumors, including those of the stomach, colon, and lung, is associated with a younger age, positive family history, and/or less accessible and detectable location, suggesting that a relatively large subgroup of cancer patients in the general population are at increased risk of cancer, even though they do not fall within a well-defined syndrome.
Microsatellite instability, in particular, requires for identification that a patient already have a tumor, because the assay compares microsatellite marker length between the monoclonal tumor cell population and normal tissue derived from the same patient. Most importantly, family history still remains the most reliable diagnostic procedure for identifying patients at risk of cancer. A molecular diagnostic approach that might identify patients with cancer or at risk of cancer, using only normal tissue, would offer a decisive advantage for intervention and treatment.
Thus, there remains a need for a diagnostic method for detecting and/or screening for the presence of diseases and/or the risk of contracting a disease. In particular, there remains a need for a method for detecting and/or screening for the presence of cancer, which does not require a tumor sample. There also remains a need for a method of detecting and/or screening for the presence of cancer and/or the risk of contracting cancer which can be applied to a wide section of the population. There also remains a need for a method of detecting and/or screening for the presence of replication error repair defects which does not require a tumor sample. There also remains a need for a method for quantifying the degree of loss of imprinting. There also remains a need for a method for screening infants for the risk of sudden infant death syndrome (SIDS). There also remains a need for kits for carrying out these methods.